Strontium substituted hydroxyapatites: Synthesis and determination of their structural properties, in vitro and in vivo performance Omer Kaygili a, ⁎, Serhat Keser b , Mustafa Kom c , Yesari Eroksuz d , Sergey V. Dorozhkin e , Tankut Ates a , Ibrahim H. Ozercan f , Cengiz Tatar a , Fahrettin Yakuphanoglu a a Department of Physics, Faculty of Science, Firat University, 23119 Elazig, Turkey b Department of Chemistry, Faculty of Science, Firat University, 23119 Elazig, Turkey c Department of Surgery, Faculty of Veterinary Medicine, Firat University, 23119 Elazig, Turkey d Department of Pathology, Faculty of Veterinary Medicine, Firat University, 23119 Elazig, Turkey e Kudrinskaja square 1-155, Moscow 123242, Russia f Department of Pathology, School of Medicine, Firat University, 23119 Elazig, Turkey abstract article info Article history: Received 20 August 2014 Received in revised form 10 April 2015 Accepted 28 May 2015 Available online 6 June 2015 Keywords: Hydroxyapatite In vitro In vivo Strontium The objective of this study is to present a detailed report related to the synthesis and characterization of strontium substituted hydroxyapatites. Based on this purpose, hydroxyapatite (HAp) bioceramics with different amounts of strontium (e.g., 0, 0.45, 0.90, 1.35, 1.80 and 2.25 at.%) were prepared using a sol–gel method. The effects of Sr sub- stitution on the structural properties and biocompatibility of the samples were studied by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) techniques, in vitro and in vivo tests. All the samples composed of the nanoparticles ranging from 21 to 27 nm. The presence of Sr at low levels influenced the crystal size, crystallinity degree, lattice parameters and volume of the unit cell of the HAp. Both in vitro conditions and soaking period in simulated body fluid (SBF) significantly affected these properties. Especially, the (Ca + Sr)/P molar ratio gradually decreases with increasing soaking period in SBF. Animal experi- ments revealed the bone formation and osseointegration for all samples, and as compared with other groups, more reasonable, were observed for the sample with the lowest Sr content. © 2015 Elsevier B.V. All rights reserved. 1. Introduction Hydroxyapatite (HAp, Ca 10 (PO 4 ) 6 (OH) 2 ), is a highly promising ceramic material due to its prominent properties such as similarity to inorganic composition of bone, non-toxicity, very high bioactivity and biocompatibility [1–5]. HAp has been synthesized by several methods including sol–gel, spray pyrolysis, combustion, hydrothermal, micro- wave, precipitation and extraction from natural resources, and the struc- tural properties of HAp can be changed and controlled by the preparation technique [6–11]. Furthermore, the doping process of HAp with different elements such as Mg, Sr, Zn, Ce, Ag, Fe and Si has been used to improve the characteristic properties of HAp [12–18]. Strontium (Sr), as a trace element in human body, improves bone strength, bone healing and microarchitecture [19]. The mechanisms for these effects were explained by enhancing preosteoblastic proliferation, bone collagen synthesis and inhibiting osteoclastic differentiation [20,21]. Taken together, Sr has been proposed as candidate agent for osseointegration [22]. Animal studies have indicated that the dosage of Sr is highly important otherwise high doses might induce osteomalacia [23]. The mechanical properties and bioactivity of the Sr-HAp coatings on the Ti–6Al–4V alloys deposited by plasma spraying technique, Sr- containing HAp/polyetheretherketone composites prepared by compres- sion molding technique and Sr-substituted HAp produced by wet chem- ical synthesis were studied by Xue et al. [24], Wong et al. [25], and Abert et al. [26], respectively. These authors reported that addition of Sr im- proved not only mechanical properties but also bioactivity of the samples. In the present study, we synthesized HAps, with low Sr content ranging from 0.45 to 2.25 at.%, by sol–gel route. The aim of this study is to investigate the effects of Sr on the crystal structure, morphology and in vitro and in vivo biocompatibility of HAp and to give a more detailed report of the as-observed results. Furthermore, the sol–gel method was chosen to synthesize all the samples because of its eminent advantages reported in the earlier studies such as high purity and low synthesis tem- perature [2,27,28]. 2. Materials and method 2.1. Synthesis All the chemicals used in the study were obtained from Sigma- Aldrich. Both pure HAp and five Sr-containing HAp samples were syn- thesized using the sol–gel technique. To prepare HAp, 0.5 M calcium Materials Science and Engineering C 55 (2015) 538–546 ⁎ Corresponding author. E-mail address: okaygili@firat.edu.tr (O. Kaygili). http://dx.doi.org/10.1016/j.msec.2015.05.081 0928-4931/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec